The history of mutational pressure changes during the evolution of adeno-associated viruses: A message to gene therapy and DNA-vaccine vectors designers

Khrustalev, Vladislav Victorovich; Khrustaleva, Tatyana Aleksandrovna; Stojarov, Aleksander Nicolaevich; Sharma, Nitin; Bhaskar, Bhaskar; Giri, Rajanish

doi:10.1016/j.meegid.2019.104100

Cited by 8 publications

(10 citation statements)

References 35 publications

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“…From this point of view, there may be such half-homogenized fragment in the ORF1a of MERS ( Figure 1C ). The “homogenization” of biases in twofold degenerate sites from third codon positions takes longer time than their “homogenization” in fourfold degenerate sites ( Khrustalev et al, 2020 ). Biases in first and second codon positions will be “improved” after an even more extended period of time ( Khrustalev et al, 2012 ).…”

Section: Resultsmentioning

confidence: 99%

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Translation-Associated Mutational U-Pressure in the First ORF of SARS-CoV-2 and Other Coronaviruses

et al. 2020

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Within 4 months of the ongoing COVID-19 pandemic caused by SARS-CoV-2, more than 250 nucleotide mutations have been detected in ORF1ab of the virus isolated from infected persons from different parts of the globe. These observations open up an obvious question about the rate and direction of mutational pressure for further vaccine and therapeutics designing. In this study, we did a comparative analysis of ORF1a and ORF1b by using the first isolate (Wuhan strain) as the parent sequence. We observed that most of the nucleotide mutations are C to U transitions. The rate of synonymous C to U transitions is significantly higher than the rate of non-synonymous ones, indicating negative selection on amino acid substitutions. Further, trends in nucleotide usage bias have been investigated in 49 coronaviruses species. A strong bias in nucleotide usage in fourfold degenerate sites toward uracil residues is seen in ORF1ab of all the studied coronaviruses: both in the ORF1a and in the ORF1b translated thanks to the programmed ribosomal frameshifting that has an efficiency of 14 – 45% in different species. A more substantial mutational U-pressure is observed in ORF1a than in ORF1b perhaps because ORF1a is translated more frequently than ORF1b. Mutational U-pressure is there even in ORFs that are not translated from genomic RNA plus strands, but the bias is weaker than in ORF1ab. Unlike other nucleotide mutations, mutational U-pressure caused by cytosine deamination, mostly occurring during the RNA plus strand replication and also translation, cannot be corrected by the proof-reading machinery of coronaviruses. The knowledge generated on the mutational U-pressure that becomes stronger during translation of viral RNA plus strands has implications for vaccine and nucleoside analog development for treating COVID-19 and other coronavirus infections.

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Section: Resultsmentioning

confidence: 99%

“…Determination of the mutational pressure direction should be a starting point in any vaccine design study ( Khrustalev et al, 2020 ). If the most frequent type of nucleotide mutation is known, one may try to choose “cold” spots for this mutation as targets for future vaccine development instead of “hot” spots.…”

Section: Discussionmentioning

confidence: 99%

Translation-Associated Mutational U-Pressure in the First ORF of SARS-CoV-2 and Other Coronaviruses

et al. 2020

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“…Determination of the mutational pressure direction should be a starting point in any vaccine design study 22 . If the most frequent type of nucleotide mutation is known, one may try to choose "cold" spots for this mutation as targets for future vaccine development instead of "hot" spots.…”

Section: Discussionmentioning

confidence: 99%

“…From this point of view, there may be such half-homogenized fragment in the ORF1a of MERS (Figure 1c). The "homogenization" of biases in twofold degenerated sites from third codon positions takes longer time than their "homogenization" in fourfold degenerated sites 22 . Biases in first and second codon positions will be "improved" after an even more extended period of time 23 .…”

Section: Nucleotide Usage Biases Along the Length Of Alpha- Beta- Gmentioning

confidence: 99%

Translation-associated mutational U-pressure in the first ORF of SARS-CoV-2 and other coronaviruses

Khrustalev

Giri

Khrustaleva

et al. 2020

Preprint

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Within four months of the ongoing COVID-19 pandemic caused by SARS-CoV-2, more than 250 nucleotide mutations have been detected in the ORF1 of the virus isolated from different parts of the globe. These observations open up an obvious question about the rate and direction of mutational pressure for further vaccine and therapeutics designing. In this study, we did a comparative analysis of ORF1a and ORF1b by using the first isolate (Wuhan strain) as the parent sequence. We observed that most of the nucleotide mutations are C to U transitions. The rate of synonymous C to U transitions is significantly higher than the rate of nonsynonymous ones, indicating negative selection on amino acid substitutions. Further, trends in nucleotide usage bias have been investigated in 49 coronaviruses species. A strong bias in nucleotide usage in fourfold degenerated sites towards uracil residues is seen in ORF1 of all the studied coronaviruses. A more substantial mutational U pressure is observed in ORF1a than in ORF1b owing to the translation of ORF1ab via programmed ribosomal frameshifting. Unlike other nucleotide mutations, mutational U pressure caused by cytosine deamination, mostly occurring in the RNAplus strand, cannot be corrected by the proof-reading machinery of coronaviruses. The knowledge generated on the direction of mutational pressure during translation of viral RNAplus strands has implications for vaccine and nucleoside analogue development for treating covid-19 and other coronavirus infections.

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“…Currently, there have been two major models to account for synonymous codon usage bias, namely the neutral (or mutational) model and the natural selective (or the translation-related selection) model. At the genomic or gene level, the mutational model has a strong correlation with genetic compositional constraints which can shape the probability of mutational fixation [17][18][19][20]. Most notably, it has been proved that elevated CpG/TpA dinucleotides content and enhanced host innate immune responses are also closely linked to synonymous codon usage [21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Dispersion of synonymous codon usage patterns in hepatitis E virus genomes derived from various hosts

et al. 2022

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Hepatitis E virus (HEV) is an important zoonotic pathogen infecting a wide range of host species. It has a positive-sense, single-stranded RNA genome encoding three open reading frames (ORFs). Synonymous codon usages of viruses essentially determine their survival and adaptation to susceptible hosts. To better understand the interplay between the ever-expanding host range and synonymous codon usages of HEV, we quantified the dispersion of synonymous codon usages of HEV genomes isolated from different hosts via V s calculation and information entropy. HEV ORFs show species-specific synonymous codon usage patterns. Ruminant-derived HEV ORFs own the most synonymous codons with stable usage patterns (V s value <0.1) which leads to the stable overall codon usage patterns (R value being close to zero). Swine-derived HEV ORFs own more concentrated synonymous codons than those from wild boar. Compared with HEV strains isolated from other hosts, the human-derived HEV exhibits a distinct pattern at the overall codon usage (R < 0). Generally, ORF1 contains more synonymous codons with stable usage patterns (V s < 0.1) than those of ORFs 2 and 3. Moreover, ORF3 contains more synonymous codons with varied patterns (V s > 1.0) than ORFs 1 and 2. The host factor serving as one of the evolutionary dynamics probably influences synonymous codon usage patterns of the HEV genome. Taken together, synonymous codons with stable usage patterns in ORF1 might help to sustain the infection, while that with varied usage patterns in ORF3 may facilitate cross-species infection and expand the host range.

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The history of mutational pressure changes during the evolution of adeno-associated viruses: A message to gene therapy and DNA-vaccine vectors designers

Cited by 8 publications

References 35 publications

Translation-Associated Mutational U-Pressure in the First ORF of SARS-CoV-2 and Other Coronaviruses

Translation-Associated Mutational U-Pressure in the First ORF of SARS-CoV-2 and Other Coronaviruses

Translation-associated mutational U-pressure in the first ORF of SARS-CoV-2 and other coronaviruses

Dispersion of synonymous codon usage patterns in hepatitis E virus genomes derived from various hosts

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